NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Uhm, try harder.

Biosimilars, by definition, use the same manufacturing process. EDEN would change the process.

From the actual MHRA guidance

Biosimilar comparability exercise

An extensive comparability exercise is required to demonstrate that the biosimilar has a highly similar quality profile when compared to the RP. This should include comprehensive analyses of the proposed biosimilar and RP, using state-of-the-art methods with suitable sensitivity and orthogonal methods to determine not only similarities but also potential differences in quality attributes. These analyses should include side-by-side comparative studies unless otherwise justified.

Quantitative ranges should be established for the biosimilar comparability exercise, where possible. These ranges should be based primarily on the quality attribute ranges measured for the RP and should not be wider than the range of variability of the RP batches (the QTPP), unless otherwise justified. The relevance of the ranges should be discussed, taking into account the number of RP batches tested, the quality attribute investigated, the age of the batches at the time of testing and the test method used. A descriptive statistical approach to establish ranges for quality attributes can be used, if appropriately justified. However, wide similarity ranges based on inappropriate statistical methods should not be used.

Ideally, batches of the biosimilar candidate would undergo analysis of biological activity (for example, cell-based assays) and in vitro functional activity at the same time as RP batches. Otherwise, an established and characterised reference standard, calibrated against international reference standards wherever possible, should be employed to minimise day-to-day assay variability.

All relevant batches of the biosimilar candidate, including clinical study batches, stability batches and process performance qualification batches (manufactured at the proposed commercial scale and site) should be analysed and compared with the RP.

Any differences detected in the quality attributes have to be appropriately justified with regard to their potential impact on safety and efficacy. It is not expected that all quality attributes of the biosimilar product are identical to the RP. However, where qualitative and/or quantitative differences are detected, these need to be justified as unlikely to impact on clinical efficacy and safety, based on characterisation and/or in vitro analysis and available literature.

Any differences which may have an impact on clinical safety and efficacy (for example, increased levels of aggregation or impurities) should be reduced by modifications in the manufacturing process, rather than being justified.

The potential impact of a different formulation/excipient(s) should be discussed in terms of product stability and compatibility, as well as clinical efficacy and safety.